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Chemical Structure| 1416992-39-6 Chemical Structure| 1416992-39-6

Structure of GC376 sodium
CAS No.: 1416992-39-6

Chemical Structure| 1416992-39-6

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GC376 is a 3CLpro (3C-like protease) inhibitor that shows promise in treating cats with certain presentations of FIP and has opened the door to targeted antiviral drug therapy.

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Product Citations

Product Citations

I. Raczkiewicz ; C. Rivière ; P. Bouquet ; L. Desmarets ; A. Tarricone ; C. Camuzet , et al.

Abstract: COVID-19 pandemic has highlighted the need of antiviral molecules against coronaviruses. Plants are an endless source of active compounds. In the current study, we investigated the potential antiviral effects of Hypericum perforatum L.. Its extract contained two major metabolites belonging to distinct chemical classes, hypericin (HC) and hyperforin (HF). First, we demonstrated that HC inhibited HCoV-229E at the entry step by directly targeting the viral particle in a light-dependent manner. While antiviral properties have already been described for HC, the study here showed for the first time that HF has pan-coronavirus antiviral capacity. Indeed, HF was highly active against Alphacoronavirus HCoV-229E (IC50 value of 1.10 µM), and Betacoronaviruses SARS-CoV-2 (IC50 value of of 0.24 to 0.98 µM), SARS-CoV (IC50 value of 1.01 µM) and MERS-CoV (IC50 value of 2.55 µM). Unlike HC, HF was active at a post-entry step, most likely the replication step. Antiviral activity of HF on HCoV-229E and SARS-CoV-2 was confirmed in primary human respiratory epithelial cells. Furthermore, in vitro combination assay of HF with remdesivir showed that their association was additive, which was encouraging for a potential therapeutical association. As HF was active on both Alpha- and Betacoronaviruses, a cellular target was hypothesized. Heme oxygenase 1 (HO-1) pathway, a potential target of HF, has been investigated but the results showed that HF antiviral activity against HCoV-229E was not dependent on HO-1. Collectively, HF is a promising antiviral candidate in view of our results and pharmacokinetics studies already published in animal models or in human.

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Product Details of GC376 sodium

CAS No. :1416992-39-6
Formula : C21H30N3NaO8S
M.W : 507.53
SMILES Code : O=S(C(O)[C@@H](NC([C@@H](NC(OCC1=CC=CC=C1)=O)CC(C)C)=O)CC2C(NCC2)=O)([O-])=O.[Na+]
MDL No. :MFCD31382192
InChI Key :BSPJDKCMFIPBAW-JPBGFCRCSA-M
Pubchem ID :71481119

Safety of GC376 sodium

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
Fcwf-4 cells 1200 μg/ml 1 hour To evaluate the virucidal activity of VRE against FIPV, the results showed that the virucidal activity of VRE was limited. PMC11078076
BHK-21 cells 50 μM, 75 μM, 100 μM 2 days Selection of 3CLpro mutations resistant to GC376 and nirmatrelvir PMC9765458
A549 cells 0.0122 to 200 μM 24 hours Test the cytotoxicity of GC376, CC50 >200 μM PMC7453019
Huh-7ACE2 cells 51 nM (EC50) 24 hours To test the inhibitory effect of GC376 on SARS-CoV-2 viral replication in Huh-7ACE2 cells, results showed that GC376 exhibited high antiviral potency PMC8989888
Vero E6 cells 0, 1, 5, 10, 50, 100, 500 µM 24 hours To evaluate the inhibitory effect of GC376 on SARS-CoV-2, the results showed EC50 values of 0.643 ± 0.085 μM and 0.881 ± 0.109 μM for HRB26 and HRB26M, respectively PMC7993387
Vero cells 0.70 μM 48 hours Evaluate the inhibitory effect of GC376 on SARS-CoV-2 replication, results showed GC376 effectively inhibited virus replication PMC7474075
Vero E6 cells 0.1 to 100 μM 48 hours Test the inhibitory effect of GC376 on SARS-CoV-2, EC50 = 0.92 μM PMC7453019
Vero E6 1.51 μM (EC50) 48 hours To evaluate the antiviral activity of GC376 against SARS-CoV-2, the results showed an EC50 of 1.51 μM. PMC8536799
Vero E6 0.068 to 0.086 μM 48 to 72 h To evaluate the inhibitory effect of GC376 and its deuterated variants against SARS-CoV-2. The results showed that deuterated variants exhibited stronger antiviral activity than GC376 in Vero E6 cells. PMC8307543
A549-ACE2 0.069 to 0.10 μM 48 to 72 h To evaluate the inhibitory effect of GC376 and its deuterated variants against SARS-CoV-2. The results showed that deuterated variants exhibited stronger antiviral activity than GC376 in A549-ACE2 cells. PMC8307543
Vero-E6 cells 2.19 ± 0.01 µM (EC50) 72 hours To evaluate the inhibitory effect of GC376 on SARS-CoV-2 viral replication, results showed that GC376 effectively inhibited viral replication PMC8016852
Vero-E6 cells 6 μM (EC50) 72 hours To test the inhibitory effect of GC376 on SARS-CoV-2 viral replication, results showed that GC376 effectively inhibited viral replication PMC8989888
Vero E6 cells 0.90 μM To evaluate the antiviral activity of Jun9-62-2R against SARS-CoV-2, showing an EC50 of 0.90 μM. PMC8672434
Caco2-hACE2 cells 2.05 μM To evaluate the antiviral activity of Jun9-62-2R against SARS-CoV-2, showing an EC50 of 2.05 μM. PMC8672434
Vero E6 cells 0.18 μM To test the inhibitory ability of GC376 against SARS-CoV-2 infection, the results showed that GC376 has significant inhibitory effects. PMC9243920

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
BALB/c mice SARS-CoV-2 infection model intramuscular injection 40 or 8 mM/l, 100 µl daily for 15 days To evaluate the in vivo antiviral efficacy of GC376 against SARS-CoV-2, the results showed that high-dose GC376 significantly reduced viral replication in the lungs but failed to completely block viral proliferation PMC7993387
Mice K18-hACE2 mice Intraperitoneal injection 100 mg/kg/day or 125 mg/kg/day Once daily for 10 days To evaluate the efficacy of deuterated GC376 variants in a lethal SARS-CoV-2 infection mouse model. The results showed that treatment significantly improved survival rates and reduced viral load and pathological changes in the lungs. PMC8307543

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.97mL

0.39mL

0.20mL

9.85mL

1.97mL

0.99mL

19.70mL

3.94mL

1.97mL

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